Short Wave - The Dubious Consent Question At The Heart Of The Human Genome Project

Episode Date: July 15, 2024

The Human Genome Project was a massive undertaking that took more than a decade and billions of dollars to complete. For it, scientists collected DNA samples from anonymous volunteers who were told the final project would be a mosaic of DNA. Instead, over two-thirds of the DNA comes from one person: RP11. No one ever told him. Science journalist Ashley Smart talks to host Emily Kwong about his recent investigation into the decision to make RP11 the major donor — and why unearthing this history matters to genetics today.Read Ashley's full article in Undark Magazine here.Questions or ideas for future episodes? Email us at [e-mail] pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. In 1990, the Department of Energy and the National Institutes of Health launched a massive undertaking called the Human Genome Project. People in the biology community and the genetics community refer to it as a moonshot for biology, if you will, kind of on par with the Apollo mission. Because for the first time ever, scientists were going to sequence the human genome as fully as possible.

That is, they were going to read all of the DNA from a person that kind of makes us a person. Ashley Smart is a senior editor at Undark Magazine, where he recently wrote about this landmark effort. Genetic sequencing and testing may be widely available nowadays. But back then, it was something wildly unprecedented and something hugely ambitious. Which is why the Human Genome Project took several scientific teams over a decade and $3 billion to complete. But there's one part of the legacy that Ashley believes doesn't get talked about enough. And that is the donors. To sequence human DNA, you need actual DNA from humans.

And so one of the questions that people have been asking pretty much since the completion of the human genome project was where did this genetic sequence come from? Who are the humans whose DNA we were looking at? And that's a complicated sort. That complicated story is the focus of Ashley's recent article in Undark Magazine, an article which investigates how the Human Genome Project veered from its initial plan in one particular way. The final genome sequence was supposed to be made up of many people's DNA, a mosaic of genetic material. But instead, 70% of the sequence comes from just one donor. and Ashley wanted to know how.

How did we end up specifically with 70%? You know, why not 100%? Why not a smaller percentage? I was curious to know why that changed. Today on the show, revisiting the ethics of the Human Genome Project. It fundamentally shifted the field of biology, but also succumbed to intense pressure along the way, resulting in an over-dependence on one anonymous male donor, RP11.

Who was he? And why does unearthing this history matter to the genetics research we do today? I'm Emily Kwong. You're listening to Shortwave, the science podcast from NPR. Ashley, take us back to the late 90s. What was the power back then of sequencing the entire human genome? What could scientists do with that information that they couldn't do before? Yeah, so a lot of people I've talked to have kind of emphasized that we didn't exactly know what the power was without having this sequence. So it was first like, can we do it at all?

Can we do it at all? And I think there was certainly an anticipation, certainly a hope that kind of understanding our genetics at this level would lead to, you know, better understanding of diseases and would lead to new medicines and treatments, treatments that can be kind of tailored to work specifically for a person based on their genetic profile. And I think, you know, it's debatable how much and to what extent the project delivered on that promise. But I think what pretty much everyone I've talked to would agree on is that the project

really launched us into a new era of biology, of the way we kind of understand living things. Yeah. And when you say genome, you're talking about all the genetic material in an organism. In this case, the organism is human beings. And that's made up of our friend DNA. I know that most people are probably aware it's like, a double helix, it's two-stranded, and it is made up of all these molecules with, like, different letters. Why would knowing the order of the letters matter? Right. So the letters

that make up our DNA, A's, C's, T's, and G's, kind of the order of those letters is basically a code for building proteins. And the proteins are kind of one of the fundamental building blocks of ourselves. They help determine things like eye color and hair color, and they perform all of these functions in cells and tissues. And so in theory, if you can understand that sequence, that code of A's, Cs, T's, and Gs, and if you can do that across all of our 23 pairs of chromosomes,

then you can unearth in what someone would call kind of a blueprint for what makes us us. But there are places where our genes vary. And so that's one of the things I think that the scientists in the Human Genome Project wanted to do. By teasing out this code, can we understand, better understand, the differences that we see when it comes to health and medicine and things related to those issues. And how they did this, you write about this in the piece, is basically by taking these blood samples. and grabbing fragments of the DNA, which they then clone. How does that work?

And why are they trying to create clones of pieces of people's DNA? Yeah, so essentially in order to sequence DNA for this project. Which is to like know the order of the letters. Yeah, to read out the order of the A-Cs and T's and Gs. You can't just stick an entire. person's DNA or chromosome through a reader and get out the whole answer that way. So you kind of have to read it in little short segments. And so they intentionally fragmented the DNA. And then they'd stick each fragment into a bacterium. And the bacteria would basically replicate that fragment as it

reproduced. And so you could basically take an entire person's genome, cut it up. up in the little pieces and then create copies of all of those pieces. It essentially let them have multiple groups around the world work on the sequencing at the same time. So in my story, I describe it as distributing identical sets of a puzzle to researchers all over the world who are really good at doing puzzles. It allows them to work on different parts of the puzzle at the same time. And then they can also check each other's work. Yeah. So at the this point in the project, it was time to recruit volunteers to the Roswell Park Cancer Institute to donate their DNA. And I understand from your piece that the consent forms at the time

said to the donors, you know, we expect no more than 10% of the final sequence to be any one volunteer's DNA. But in reality, what ended up happening is one person's DNA made up the bulk of the final sequence. Ashley, how did that happen? So it's complicated and different people that I've talked to have given me different answers. But what seems to be clear is that sometime after March 1997, after that recruitment process, the project shifted course. And it decided that the mosaic genome that it had aspired to was either not going to be feasible and not going to be practical. And it decided to shift to focusing on primarily one donor. Why did they shift course? Well, some people I've talked to have told me that there were technical reasons, that there was a worry that those places where our DNA differs could create challenges when you're trying to stitch together a coherent genome.

But other people I've talked to have pointed to time being the bigger issue. And one of the important developments here was that in an early 1998, the Human Genome Project got competition, essentially. from the private sector. So there was Craig Venter, who is kind of a noted scientist and entrepreneur, and who had actually done some work with the Human Genome Project in the early days. He kind of splintered off

and announced a new private project that would be done with a company called Solarigenomics, and they said that they were going to complete the genome even faster than the Human Genome Project and at a lower cost. And so people I've talked to said that really lit a fire under the Human Genome Project to say, how can we do this thing faster? But did any of the donors know about this shift in focus to one person's DNA being most of the data?

None of the Roswell Park donors know. And so RP11, the anonymous male donor who makes up 70 to 75% of the genome, was never told of this change. And to this day, does he have any idea? I haven't spoken to him, so I don't know. But I know that to this day, Francis Collins, who led the project, never attempted to tell RP 11 of this change. And I should point out that there was an ethics panel, an institutional review board, who basically decided that none of the donors should be told about this change. Tell me more about what we know about RP 11.

Yeah, so years after the human genome project ended, this sequence that came out of it remained kind of a central resource in genetics and has been the subject of a ton of analysis and study. And one of those studies that was done in 2010 analyzed the sequence, what we call the reference genome, and concluded that RP11, just based on the genetic patterns they saw in his sequence, showed a mix of African ancestry and European ancestry, consistent with likely identifying as African American.

And so when I thought about RP11 and how they might feel, knowing that their genome, one, played such an important part in the, the march of genetic science. And two, you know, when they realized that what the project scientist did was something different than what they told them, you know, those realizations were colored by the fact that, you know, there's kind of a long history of tension and ethical missteps, maybe even say ethical mistreatment or ethical wrongs being done to the African-American community here. And me as a black person who cover science and was once upon a time ago a scientist. When I think about RP11 possibly being

a black person who made this big contribution to science, I think about myself when I think about him, you know, and I think about kind of this big contribution hasn't been acknowledged, right? And it may be the case that RP 11 doesn't want it to be acknowledged. It may be the case that RP 11 would rather know and know that he was behind this genome. But I guess I feel sympathetic for him and want for him to at least be able to make that choice for himself. Yeah. You quote many of the scientists involved, and the one that really keeps sticking with me is Aristheris Patrinos. who says to you, I think at this point, it probably would be a good idea to come out in the open and tell everybody what happened and give as many specifics as possible.

How does society stand to benefit from knowing fully the story of the human genome project? I mean, as a journalist, I feel like my goal is always to tell a true story and to help provide an honest record of what happened. this is, you know, an aspect of the project that had never really been documented for the record, and I wanted to do that. And so I guess one hope that I would have, you know, for this piece would be to kind of foster more of a discussion between people who are thinking about genomics from a very technical point of view and the people who are thinking about the ethics of how we do this work. I think really for the field to thrive both of those communities. probably need to be talking openly with each other and also respecting what the other side has to say. Ashley Smart is the Associate Director

of the Night Science Journalism Program at MIT and a senior editor at Undark. Thank you so much for coming on Fort Wave to talk about this reporting you did. Thank you so much for having me. And you can read The Piece Yourself. We highly encourage it at the link in our show notes. This episode was produced by Burley McCoy.

It was edited by our show, runner Rebecca Ramirez, and fact-checked by Burley and Rebecca. The audio engineer was Kwayzee. Beth Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting strategy. I'm Emily Kwong. Thanks for listening to Shortwave from NPR.